Respiratory syncytial virus (RSv) is the primary etiologic agent of pediatric respiratory tract infection. In premature infants and children with bronchopulmonary dysplasia or congenital heart disease, RSv induced pneumonia and bronchiolitis cause significant morbidity and mortality. Prophylactic RSv vaccines are not available and the use of Ribavirin, an approved treatment for RSv infection, has proven to be controversial. Currently the most promising approach to prophylaxis and treatment of RSv disease in high risk cases is passive immunization. A hyperimmune intravenous immuneglobulin (IVIG) product for the prevention of RSv disease has been shown to be extremely effective in a Phase III clinical trial. The development of a standardized, defined product with higher specific activity would lower costs and enhance ease of administration and thus have increased use in populations at risk. The objectives of this Phase I proposal is to generate potent neutralizing human monoclonal antibodies to the more conserved fusion (F) glycoprotein of RSv in the HyPBL-SCID mouse (severe combined immunodeficient mice reconstituted with human Peripheral blood lymphocytes) immunized with RSv. Selection of antibodies by their ability to neutralize a panel of clinical isolates in vitro and in vivo models will form the basis of a Phase II study.